Glucagon gene sequence. Four of six exons encode separate functional domains of rat pre-proglucagon.

Glucagon, a peptide of 29 amino acids that is produced and secreted by the pancreas, is a regulator of carbohydrate and protein metabolism. Recently, we determined the nucleotide sequence of a mRNA of 1300 nucleotides that encodes rat pre-proglucagon, a polyprotein precursor of glucagon. The polyprotein contains the sequences of glucagon and two glucagon-like peptides arranged in tandem and separated by intervening peptides. Now we report the structure of the gene encoding rat pre-proglucagon. The unique transcriptional unit of the gene spans 10 kilobase pairs and consists of six exons and five introns. Four of the six exons encode distinct functional domains of the pre-proglucagon. The signal sequence, glucagon, and two glucagon-like sequences arranged in tandem are each encoded by a separate exon. A promoter sequence TA-TAAA is located 26 base pairs upstream from the mRNA cap site, and two polyadenylation signals AA-TAAA are present in the 3' untranslated region of the encoded mRNA. The 3' flanking region of the gene contains repetitive sequence DNA.